Donald K. Corle

LACK OF EFFECT OF A LOW-FAT, HIGH-FIBER DIET ON THE RECURRENCE OF COLORECTAL ADENOMAS

BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers. METHODS We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization. RESULTS A total of 1905 of the randomized subjects (91.6 percent) completed the study. Of the 958 subjects in the intervention group and the 947 in the control group who completed the study, 39.7 percent and 39.5 percent, respectively, had at least one recurrent adenoma; the unadjusted risk ratio was 1.00 (95 percent confidence interval, 0.90 to 1.12). Among subjects with recurrent adenomas, the mean (+/-SE) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group. The rate of recurrence of large adenomas (with a maximal diameter of at least 1 cm) and advanced adenomas (defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia, including carcinoma) did not differ significantly between the two groups. CONCLUSIONS Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas.

Lack of Effect of a Low-Fat, High-Fruit, -Vegetable, and -Fiber Diet on Serum Prostate-Specific Antigen of Men Without Prostate Cancer: Results From a Randomized Trial

PURPOSE To determine whether a diet low in fat and high in fruits, vegetables, and fiber may be protective against prostate cancer by having an impact on serial levels of serum prostate-specific antigen (PSA). METHODS Six hundred eighty-nine men were randomized to the intervention arm and 661 to the control arm. The intervention group received intensive counseling to consume a diet low in fat and high in fiber, fruits, and vegetables. The control group received a standard brochure on a healthy diet. PSA in serum was measured at baseline and annually thereafter for 4 years, and newly diagnosed prostate cancers were recorded. RESULTS The individual PSA slope for each participant was calculated, and the distributions of slopes were compared between the two groups. There was no significant difference in distributions of the slopes (P =.99). The two groups were identical in the proportions of participants with elevated PSA at each time point. There was no difference in the PSA slopes between the two groups (P =.34) and in the frequencies of elevated PSA values for those with elevated PSA at baseline. Incidence of prostate cancer during the 4 years was similar in the two groups (19 and 22 in the control and intervention arms, respectively). CONCLUSION Dietary intervention over a 4-year period with reduced fat and increased consumption of fruits, vegetables, and fiber has no impact on serum PSA levels in men. The study also offers no evidence that this dietary intervention over a 4-year period affects the incidence of prostate cancer during the 4 years.

Self-rated quality of life measures: Effect of change to a low-fat, high-fiber, fruit and vegetable enriched diet

The Polyp Prevention Trial (PPT) was a multicenter, randomized clinical trial to determine the effect of a low-fat (20% of energy from fat), high-fiber (18 g/1000 kcal/day), high-fruit/vegetable (3.5 servings/1000 kcal/day) eating plan on the recurrence of large bowel adenomatous polyps. The PPT provided an opportunity to examine the impact of dietary changes on quality of life. At baseline and annually for 4 years, participants in the Quality of Life Substudy of PPT completed a Quality of Life Factors (QF) Questionnaire, a modified Block-National Cancer Institute Food Frequency Questionnaire, and a Health and Lifestyle Questionnaire. The 51-item QF Questionnaire assessed changes in nine domains: taste, convenience, cost, self-care, social, health assessment, health belief, health action, and life satisfaction. The analysis compared annual changes in domain scores for intervention (n = 194) and control (n = 200) participants. At Year 1, 363 (92%) completed a questionnaire, and 325 (82%) participants completed a Year 4 questionnaire. There were no statistically significant differences between treatment groups in the change from baseline to Year 1 for the convenience, cost, taste, health assessment, and life satisfaction domains. At Year 1, intervention participants rated the self-care (p < .001), health belief (p = .021), and health action (p < .001) domains significantly higher and the social domain significantly lower (p < .001) than control participants. These changes were consistent through Years 2, 3, and 4. This study

Comparison of pulsatile subcutaneous gonadotropin-releasing hormone and exogenous gonadotropins in the treatment of men with isolated hypogonadotropic hypogonadism

Eight men with isolated hypogonadotropic hypogonadism were treated with pulsatile gonadotropin-releasing hormone (GnRH) after maximal testicular growth and function had already been achieved with human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG). Only four subjects could normalize plasma testosterone (T) levels (group A). After 18 months of GnRH therapy, testicular size of group A increased by 53% (P less than 0.01) over that previously attained with exogenous gonadotropins. However, despite further testicular growth, two men who were previously azoospermic on hCG/hMG remained so on GnRH. In the other two patients, total sperm count increased minimally. Thus, pulsatile gonadotropin levels achieved with GnRH are more effective in stimulating testicular growth, but not necessarily sperm output, than are stable gonadotropin concentrations obtained with hCG/hMG.

The efficiency of the matched-pairs design of The Community Intervention Trial for Smoking Cessation (COMMIT)

The Community Intervention Trial for Smoking Cessation (COMMIT) was a randomized trial to evaluate the effects of a community-wide smoking cessation intervention on smoking behavior. The statistical design involved 22 pair-matched communities and the randomization of one community in each of the 11 pairs to the intervention, with the other community in the pair acting as a comparison. Communities were matched on the basis of their geographical proximity and similarity of demographic composition. In this paper, we use the data on the rates of quitting smoking among cohorts of heavy and light/moderate smokers in each community to estimate the gains in efficiency achieved by the matched-pairs design compared to an unmatched randomized trial. We find evidence of some gain in efficiency, although the data are not extensive enough to give estimates of efficiency gain that have good precision.

Measuring cell proliferation in the rectal mucosa: comparing bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) assays

Cell proliferation in the human colorectum can be measured using bromodeoxyuridine (BrdU) or proliferating cell nuclear antigen (PCNA) assays. Using data from the National Cancer Institutes Polyp Prevention Trial, these two assays are compared using correlation coefficients and variance components analysis. Adjusting for fixed as well as for the random effects of between-biopsy and scoring variation, the estimated correlation is 0.46 for the log labeling index and 0.45 for log proliferative height. This is an estimate of the highest correlation that can be achieved by taking multiple biopsies scored by multiple scorers. For single biopsies, the estimated correlation is 0.16 and 0.10, respectively. There are significant differences between the variance components for the two assays. For example, for log labeling index, PCNA has a lower variation between biopsies than BrdU, but higher variation between scorings. When used in a clinical or epidemiological setting, it is important to take multiple biopsies at multiple time points.

Abstract PL06-02: Patient navigation and timeliness of diagnostic evaluation: Results from the Patient Navigation Research Program

Background: Patient navigation has been proposed as a means to reduce cancer health disparities, through the addition of a trained navigator to the health care team. Patient navigators help patients to identify barriers to receiving needed care, and to develop individually targeted plans to overcome these barriers. The Patient Navigation Research Program is a nine-site program to evaluate the benefit of patient navigation among underserved populations from diverse socioeconomic and geographic locations within the United States. Methods: Patients with breast, cervical, colorectal or prostate screening abnormalities were eligible for enrollment. The primary outcome was time to diagnostic resolution of the screening abnormality, assessed dichotomously as resolved or not within 365 days, and analyzed using survival curves and Cox proportional hazards models of time to resolution by 12 months. Due to the differing study designs at the 9 sites (RCT, Group randomized, and non randomized group allocation) we calculated an effect size for each cancer type for each site, and utilized a meta-analysis to assess an overall effect size. Models were adjusted for age, race, insurance and marital status. Results: There were 10,513 subjects (5,055 Navigated and 5,458 Non-navigated) recruited from the 9 sites, 64% with breast cancer screening abnormalities. The study population was diverse with 74% from minority groups (32% African American, 39% Latino, 4% other), and low income with 17% Medicaid insured, and 32% with no insurance. In the control population, 62% to 95% of the participants did not reach diagnostic resolution after their abnormal screening result within 12 months. Those in the navigation arm were more likely to reach resolution after an abnormal test in 13 of the 15 cancer sites, (89 to 99% resolved). Of the 15 hazard rate ratios, 11 showed a statistically significant positive effect of the navigation intervention, 3 others showed a non statistically significant benefit of navigation, and 1 showed a negative effect of navigation on time to diagnostic resolution, (effect sizes ranging from an adjusted HR of 0.38 to 3.94, with a higher HR favoring the navigation arm). Implications: Compared to non-navigated subjects, participants with an abnormal cancer screening test who were allocated to receive a patient navigation intervention were more likely to receive timely diagnostic resolution of their abnormal screening test. Patient navigation for vulnerable populations may be beneficial in reducing cancer disparities. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL06-02.